The overall purpose of the proposed research is to study corneal uptake and metabolism of topically applied retinoids with regard to their efficacy in the treatment of xerophthalmia and promotion of corneal would healing. The study will consist f four main components. First, using both normal and vitamin A deficient rabbits, the rates of penetration and uptake of 3H-retinol and 3H-retinoic acid will be determined in isolated perfused corneas and in situ following topical application of these retinoids to the cornea. These studies will include determination of specific versus nonspecific uptake of retinoids and a comparison of uptake of free retinol to uptake of retinol bound to retinol binding protein. Radioautography and scintillation counting will be used to localize 3H-retinoids inthe various layers of the cornea. Second, the component layers of normal or vitamin A deficient corneas will be extracted with methanol after exposure to retinol or retinoic acid in vitro or in situ and these extracts will be analyzed for metabolites and breakdown products by high performance liquid chromatography. All studies using xerophthalmic rabbits will include the early and later stages of the disease, including punctate keratopathy, early keratinization and severe xerosis. Third, retinol and retinoic acid will be applied topically to rabbit corneas wounded by scrapig or by a heptanol burn to determine whether this treatment will increase the rate of corneal wound healing. After healing the permeability and uptake characteristics for retinoids of the re-epithelialized corneas will be compared to those of normal corneas. Fourth, retinoid uptake characteristics of normal and vitamin deficient lens will also be investigated.